The mammalian hippocampal formation is critical for memory storage and retrieval and for navigation. Over the past several decades the discoveries of place cells, head direction cells and grid cells have begun to elucidate the mechanisms for these processes. The idea has emerged that the hippocampal formation creates a rigid, two-dimensional framework upon which specific objects, places and events can be registered. The registration of sensory data on the inherent framework appears to be critical for both memory and navigation. Grid cells of the medial entorhinal cortex are the core of the proposed framework. The spatial firing pattern of a single grid cell, with bumps distributed at regular distances from one another and patterned in a triangular lattice, suggests the nature of the 2D representation. While we have begun to understand the nature of individual grid cells, little is known about how grid cells within medial entorhinal cortex relate and connect to one another to form a network. Emerging evidence suggests that within a small region of entorhinal cortex grid cells form a "module" where all of the cells have identical scale and orientation. While it is clear that this is roughly true for broad regions, it is not clear if there are what we call "rigid modules": that is, sets of grid cells with identical scale and orientation, where the spatial offsets among members are fixed across all environments. Characterization of the modular organization of the entorhinal cortex is a critical step in elucidating the inherent framework that is the core of hippocampal processing. Characterizing modules is the goal of the proposed studies. The first group of studies (strategic aims 1) is aimed at mapping hippocampal modules and exploring the extent that the modules may be rigid. We will make simultaneous recordings of grid cells within a small region (off of single tetrodes) and across broader regions (across tetrodes) to see whether the grid scale and orientations of the simultaneously recorded cells are fixed locally or across broader regions. Since we are particularly interested in whether pairs of cells are part of a rigid set, we will explore whether the spatial offsets of their grid bumps are fixed across broad regions of environmental space and across environments. The second study (strategic aim 2) will make a critical test for the existence of rigid modules. The strategy is to create a situation where grid cell firing drifts, due to lack of sensory cues, and to see whether firing patterns are maintained and pairs of grid cells drift together. Part one involves creating a sensory-deprived environment and establishing that it is sufficient to get reliable grid-cell drift. In part 2 we will control for drift and see whether within and across cell firing patterns remain stable and rigid. PUBLIC HEALTH RELEVANCE: Normal functioning of the hippocampus is critical for navigation and memory. Understanding processing within the hippocampal formation may shed light on disorders involving the hippocampal formation and lead to the treatment of these disorders. Disorders and diseases that affect the hippocampus include Alzheimer's disease, temporal lobe epilepsy, post-traumatic stress disorder and learning disorders.